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Table 5 Selected relevant pre-clinical studies based on recent MNPs for the diagnosis and treatment of AD

From: Nanomedicine-based technologies and novel biomarkers for the diagnosis and treatment of Alzheimer’s disease: from current to future challenges

Loaded molecule

Metal core

Surface modifications

Dose

Admin. route

In vitro/in vivo Model

Results

Refs

Iron oxide

NIR Fluorescent probe

10 ng/mL

Incubation

Aβ42 induced

SH-SY5Y cells

MNPs can simultaneously perform in vivo NIR fluorescence and magnetic resonance imaging of Aβ plaques in the brain of transgenic mice, prevent Aβ aggregation, disaggregate preformed Aβ fibrils and play a protective effect on the toxicity of human neuroblastoma cells induced by Aβ42

Cai et al. [201]

0.2 mmol Fe/kg

i.v

APP/PS1 mice

Iron oxide

chitosan

NA

Exposition

Synthetic urine

MNPs were used to fabricate a highly sensitive AChE electrochemical biosensor. The novel biosensor exhibits the lower limit of detection of ACh that has been reported in the literature. It also shows good recoveries in the determination of ACh in synthetic urine

da Silva et al. [192]

Selenium

Chondroitin sulfate

1.45 µg/mL

Incubation

SH-SY5Y cells

MNPs inhibit Aβ aggregation, protect SH-SY5Y cells from Aβ42-induced cytotoxicity, decrease okadaic acid-induced actin cytoskeleton instability, In addition, decrease the levels of ROS and MDA, increase the levels of GSH-Px, and attenuate the hyperphosphorylation of tau by regulating the expression of GSK-3b

Gao et al. [195]

Cerium dioxide

Zirconium

4 mg/m3 for 3–5 h/day

i.n

5xFAD mice

ApoE-/- mice

The inhalation exposure to the MNPs promotes changes in forced motor performance and exploratory motor activity in ApoE-/- and 5xFAD mice, respectively

Wahle et al. 2020

Quercetin

Gold / Palladium

Polysorbate 80

5–40 µg/mL

Incubation

SH-SY5Y cells

MNPs activate autophagy of SH-SY5Y cells, promote the fusion of autophagosomes and lysosomes, accelerate the clearance of Aβ, and protect SH-SY5Y cells from Aβ -induced cytotoxicity damage. MNPs are not toxic both in vitro and in vivo

Liu et al. [194]

1 mg/kg

i.v

Nude mice

Iron oxide

Cadmium sulfide

F. oxysporum and Verticillium sp. proteins

5 − 100 μg/mL

incubation

Neuro2a cells

MNPs do not affect the viability of neuroblastoma cells and show dual properties of inhibition and disaggregation of Tau fibrillar aggregates

Sonawane et al. [198]

Palladium

Bioactive Hydrogen

6.25–25 µg/ml

incubation

N2a-SW cells

Developed MNPs are able to recover mitochondrial dysfunction, inhibit Aβ generation and aggregation, block synaptic and neuronal apoptosis and promote neuronal energy metabolism by eliminating oxidative stress and activating the anti-oxidative pathway, consequently ameliorating the cognitive impairment in AD mice

Zhang et al. [200]

2µL of MNPs (0.5–2 mg/ml)

Stereotaxic injection

APP/PS1 mice

Silver

PrP95-110

1.2 nM

Incubation

Aβ enriched CSF and serum

Authors report an electrochemical method for the detection of Aβ oligomer with a peptide as the bio-receptor and silver MNPs aggregates as the redox reporters

Xing et al. [193]

CQ

Gold

0.5 mg/mL

Incubation

PC12 cells

In this system, CQ is released only upon exposure to conditions in which H2O2 levels are high, such as those in Aβ plaques. NPs inhibit Aβ40 aggregation, and reduce the cell membrane disruption, microtubular defects and ROS-mediated apoptosis

Yang et al. [199]

5, 10, 20 mg/kg

i.v

ICR mice

  1. Ach, acetylcholine; CQ, metal chelator Clioquinol; CSF, cerebrospinal fluid; GSH-Px, glutathione peroxidase; MDA, malondialdehyde; NIR, phenothiazine-based near-infrared fluorescent dye; PrP95-110, cellular prion protein; ROS, reactive oxygen species; STZ, streptozotocin